Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Int J Pharm. 2021 Jul 15;604:120722. doi: 10.1016/j.ijpharm.2021.120722. Epub 2021 May 20.
The aim of this work is to co-load paclitaxel (PTX) and etoposide (ETP) in methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (mPEG-PLGA NPs) to overcome pharmacokinetics and physiological limitations and enhance therapeutic efficacy for treating intracranial glioblastoma. Both drugs were loaded into mPEG-PLGA NPs by a nano-precipitation method. The resultant NPs demonstrated an enhanced cytotoxic effect indicated by lower IC values and augmented cell apoptosis to U87 and C6 glioma cell lines compared to both free drugs. Additionally, blood compatibility assays showed that the PTX/ETP co-loaded mPEG-PLGA NPs did not induce blood hemolysis, blood clotting, or platelet aggregation. In vivo anti-glioma efficacy evaluation in rats bearingintracranialC6glioma revealed a superior anti-glioma activity for the treatment with PTX/ETP co-loaded mPEG-PLGA NPs compared to other formulations, particularly a significantly longer median survival, 76 days compared to 36 days for free PTX and 37 days for free ETP treatment, respectively, and higher tumor regression, proved by magnetic resonance imaging (MRI).
这项工作的目的是将紫杉醇（PTX）和依托泊苷（ETP）共同载入甲氧基聚乙二醇-聚（乳酸-共-乙醇酸）纳米粒（mPEG-PLGA NPs）中，以克服药代动力学和生理限制，提高治疗颅内神经胶质瘤的疗效。两种药物均通过纳米沉淀法载入 mPEG-PLGA NPs。与游离药物相比，所得 NPs 表现出增强的细胞毒性作用，IC 值更低，诱导 U87 和 C6 神经胶质瘤细胞凋亡的作用增强。此外，血液相容性试验表明，PTX/ETP 共载 mPEG-PLGA NPs 不会引起血液溶血、凝血或血小板聚集。荷颅内 C6 神经胶质瘤大鼠的体内抗神经胶质瘤疗效评价表明，与其他制剂相比，PTX/ETP 共载 mPEG-PLGA NPs 的抗神经胶质瘤活性更优，特别是中位生存期显著延长，分别为 76 天，而游离 PTX 为 36 天，游离 ETP 为 37 天，肿瘤消退率更高，这一点通过磁共振成像（MRI）得到了证实。
